Acyclic nucleoside phosphonates (ANPs) represent a class of nucleotide analogues in which a phosphonate group is linked to the alkyl side chain of various purines and pyrimidines. This class of nucleoside analogues possesses broad-spectrum antiviral activity, together with a high level of selectivity in vitro and in vivo. Among them adefovir chemically 9-(2-phosphonylmethoxyethyl)adenine and its ester derivatives (described in U.S. Pat. No. 4,808,716), tenofovir chemically (R)-9-(2-phosphonomethoxypropyl) adenine and its ester derivatives (described in U.S. Pat. No. 5,922,695) are having potent and selective activity against HIV and other retroviruses such as retro-, herpes- and hepadnaviruses.
Tenofovir disoproxil is represented by the following structure of formula 1:
Adefovir dipivoxil is represented by the following structure of formula 2:

These compounds are normally prepared by the esterification of phosphonic acid of formula 3:
wherein R′ is alkyl or H;with an appropriate halide to obtain the compounds such as those shown in formula 2 and 3.
It has been found that introduction of groups such as isopropyloxycarbonyloxy methyl or pivaloyloxy methyl group to phosphonic acid compounds of formula 3 for the preparation of the phosphonic acid bis ester compounds such as tenofovir disoproxil of formula 1 or adefovir dipivoxil of formula 2 is associated with the problem of alkylation of N4-amine group to form corresponding N-alkylated impurities. Excess use of alkylating agents leads to the formation of N4-alkylated impurity. Similarly the use of lower quantities of alkylating agents leads to lower yields of products like tenofovir disoproxil and adefovir dipivoxil and formation of higher amounts of the corresponding mono ester impurities.
In an effort to solve the above said problems, we have succeeded in finding protecting agents that are advantageous in that a) the said protecting agents can successfully protect amino group and at the same time do not form esters with phosphonic acid group of the compound of formula I:
b) when the amine group is once protected with these protecting groups, then desired esterification can be carried out; and c) then the said protecting group can be removed under conditions that does not hydrolyse or solvolyse the ester groups.